Photodynamic Therapy Activity Research Articles

Combination of MHI148 Targeted Photodynamic Therapy and STING Activation Inhibits Tumor Metastasis and Recurrence.

Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after conventional treatments, its effectiveness remains constrained by significant challenges, such as impaired antigen presentation by dendritic cells (DCs) and inadequate T cell infiltration into tumor tissues. To address these limitations, we developed a multifunctional nanoparticle platform, termed GM@P, which consisted of a hydrophobic shell encapsulating the photosensitizer MHI148 and a hydrophilic core containing the STING agonist 2'3'-cGAMP. This design elicited robust type I interferon responses to activate antitumor immunity. The GM@P nanoparticles loaded with MHI148 specifically targeted breast cancer cells. Upon exposure to 808 nm laser irradiation, the MHI148-loaded nanoparticles produced toxic reactive oxygen species (ROS) to eradicate tumor cells through photodynamic therapy (PDT). Notably, PDT stimulated immunogenic cell death (ICD) to foster the potency of antitumor immune responses. Furthermore, the superior photoacoustic imaging (PAI) capabilities of MHI148 enabled the simultaneous visualization of diagnostic and therapeutic procedures. Collectively, our findings uncovered that the combination of PDT and STING activation facilitated a more conducive immune microenvironment, characterized by enhanced DC maturation, infiltration of CD8+ T cells, and proinflammatory cytokine release. This strategy stimulated local immune responses to augment systemic antitumor effects, offering a promising approach to suppress tumor growth, inhibit metastasis, and prevent recurrence.

Revolutionizing medicine: Molecularly imprinted polymers as precision tools in cancer diagnosis and antibiotic detection.

Molecularly imprinted polymers (MIPs) are pivotal in medicine, mimicking biological receptors with enhanced specificity and affinity. Comprising templates, functional monomers, and cross-linkers, MIPs form stable three-dimensional polymer networks. Synthetic templates like glycan and aptamers improve efficiency, guiding the molecular imprinting process. Cross-linking determines MIPs' morphology and mechanical stability, with printable hydrogels offering biocompatibility and customizable properties, mimicking native extracellular matrix (ECM) microenvironments. Their versatility finds applications in tissue engineering, soft robotics, regenerative medicine, and wastewater treatment. In cancer research, MIPs excel in both detection and therapy. MIP-based detection systems exhibit superior sensitivity and selectivity for cancer biomarkers. They target nucleic acids, proteins, and exosomes, providing stability, sensitivity, and adaptability. In therapy, MIPs offer solutions to challenges like multidrug resistance, excelling in drug delivery, photodynamic therapy, photothermal therapy, and biological activity regulation. In microbiology, MIPs serve as adsorbents in solid-phase extraction (SPE), efficiently separating and enriching antibiotics during sample preparation. They contribute to bacterial identification, selectively capturing specific strains or species. MIPs aid in detecting antibiotic residues using fluorescent nanostructures and developing sensors for sulfadiazine detection in food samples. In summary, MIPs play a pivotal role in advancing medical technologies with enhanced sensitivity, selectivity, and versatility. Applications range from biomarker detection to innovative cancer therapies, making MIPs indispensable for the accurate determination and monitoring of diverse biological and environmental samples.

Synthesis and biological properties of axially bis − (3,4,5-trimethoxybenzyloxy) phthalocyaninato silicon (IV)

In this study, bis − (3,4,5-trimethoxybenzyloxy) phthalocyaninato silicon (IV) was obtained from the reaction of 3,4,5-trimethoxybenzyl alcohol with SiPcCl2. This phthalocyanine was characterized using 1H NMR, FTIR, UV–vis and mass spectra. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, antidiabetic, deoxyribonucleic acid (DNA) cutting, biofilm inhibition, anti-microbial and antimicrobial photodynamic therapy (aPDT) activities of newly synthesized bis − (3,4,5-trimethoxybenzyloxy) phthalocyaninato silicon (IV) molecule were studied. The best activities were 41.58 % at 100 mg/L for antioxidant and 41.66 % for antidiabetic at 400 mg/L concentration. The molecule degraded the biofilm matrix formed by Pseudomonas aeruginosa and Staphylococcus aureus as 78.61 % and 89.26 %, at 50 mg/L concentration, respectively. It was observed that E. coli, which was used as a model microorganism, was inhibited at a level close to 100 % even at the lowest concentration of 50 mg/L. While double strand break was observed at 50 mg/L DNA cutting activity, it was determined that DNA was reduced to nucleotides at 100 and 200 mg/L. The Pc also displayed effective antimicrobial and aPDT abilities against pathogens. With the application of aPDT, the effectiveness of antimicrobial activity increased 2 to 4 times. These increase rates are very important. The main conclusion of the study was that the newly synthesized compound exhibited various effective biological activities such as effective antioxidant, antidiabetic, DNA cleavage, antimicrobial, aPDT, biofilm inhibition and microbial cell viability inhibition.

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid.

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.

Zinc-Substituted Hemoglobin-Albumin Cluster as a Porphyrin-Carrier for Enhanced Photodynamic Therapy.

Apohemoprotein is focused on the field of theranostics, serving as a porphyrin carrier. Hemoglobin (Hb) consists of α2β2 tetramer with iron(II)-protoporphyrin IX (heme) bound to each globin. However, heme-removed Hb (apoHb) causes dissociation at αβ interfaces and aggregation under physiological conditions. We synthesized a stable apoHb derivative comprising intramolecular-crosslinked apoHb (apoXHb) and human serum albumin (HSA), apoXHb-HSA3. ApoXHb-HSA3 engendered no aggregates in the physiological solutions. Moreover, apoXHb-HSA3 was reconstituted with zinc(II)-protoporphyrin IX (ZnP), generating ZnXHb-HSA3, a potent photosensitizer for photodynamic therapy (PDT). The photophysical properties of ZnXHb-HSA3 were identical to those of zinc-substituted XHb (ZnXHb). Cellular uptake behavior was evaluated using various cancer cell lines. ZnXHb-HSA3 released ZnP around the cells, and the free ZnP penetrated cell membranes. In contrast, protein units were not observed within the cells. ZnXHb-HSA3 showed no cytotoxicity under dark conditions and demonstrated superior PDT activity in comparison to naked ZnXHb. ZnXHb-HSA3 acts as an innovative porphyrin carrier for enhanced PDT.

Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.

Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 μM; MCF-7, IC50 = 43.30 ± 1.76 μM; A375, IC50 = 28.03 ± 1.00 μM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 μM). At a concentration of 80 μM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.

Effects of metalation on the PDT activity of arene ruthenium porphyrin-based photosensitizers on prostate cancer

SignificanceProstate cancer is a major health issue (second most common cancer in men worldwide). Despite therapeutic advances and early detection, many side effects are often observed during treatment. Photodynamic therapy (PDT) is a promising therapy to reduce side effects, many 2nd and 3rd generation of photosensitizer (PS) are poorly soluble in aqueous media, limiting their attractiveness. ApproachWe have developed and tested 3rd generation of PS vectorized by arene-ruthenium (Ru) complexes coordinated to tetrapyridylporphin (tpp-2H), Zn-tetrapyridylporphin (tpp-Zn) or Co-tetrapyridylporphin (tpp-Co). ResultsTwo of the three complexes show a good efficacy. The compounds localize into the cytoplasm. An analysis of the apoptotic process shows a cleavage of poly-ADP ribose polymerase (PARP) and a strong induction of DNA fragmentation following irradiation. ConclusionsArene-ruthenium tetrapyridylporphin complexes are excellent candidates for PDT application. The addition of the metal shows a decrease (tpp-Zn) or no effects (tpp-Co), compared to the metal free photosentizer (tpp-2H).

Synergistic effect of mesoporous silica nanocarrier-assisted photodynamic therapy and anticancer agent activity on lung cancer cells

Investigating combined treatment methodologies is crucial for addressing the complex nature of cancer. As an emerging strategy, nano-biotechnology encourages the design of unique nanocarriers possessing simultaneous therapeutic application properties. This study aims to explore the combined effects of photodynamic and anticancer treatments using a multifunctional nanocarrier system co-administering the photosensitizer IR780 and the anticancer agent curcumin (Cur) on lung cancer cells. Nanocarriers were prepared by encapsulation IR780 and Cur inside polyethylene glycol-capped mesoporous silica nanoparticles (Cur&IR780@MSN). Various concentrations of nanocarriers were evaluated on A549 cells following 5 min NIR laser light (continuous wave, 785 nm, 500 mW/cm2) irradiation. The internalization of nanocarriers was observed through the fluorescence of Cur. Changes in cell viability were determined using the MTT assay and AO/PI staining. A scratch assay analysis was also performed to examine the impact of combined treatments on cell migration. Characterization of the nanocarriers revealed adequate hydrophobic drug loading, temperature-inhibited feature, enhanced reactive oxygen species generation, a pH-dependent curcumin release profile, and high biocompatibility. Cur&IR780@MSN, which enabled the observation of synergistic treatment efficacy, successfully reduced cell viability by up to 78%. In contrast, monotherapies with curcumin-loaded nanocarriers (Cur@MSN) and IR780-loaded nanocarriers (IR780@MSN) resulted in a 38% and 56% decrease in cell viability, respectively. The constructed Cur&IR780@MSN nanocarrier has demonstrated remarkable performance in the application of combination therapies for lung cancer cells. These nanocarriers have the potential to inspire future studies in tumor treatment methods.

Antimicrobial activity of cationic water-soluble porphyrin against multidrug-resistant bacteria in biofilms and canine skin samples.

Multidrug-resistant (MDR) microorganisms pose a threat to animal health, particularly in integumentary diseases, which can be caused by multiple organisms and often manifest as biofilms, hindering treatment effectiveness. We evaluated the antimicrobial activity of antimicrobial photodynamic therapy (aPDT) using a water-soluble tetra-cationic porphyrin (4-H2TMeP) against MDR bacteria cultured in biofilm and in mono and polyculture grown on canine skin samples. We utilized 4-H2TMeP porphyrin against MDR Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus pseudintermedius. A non-cytotoxic concentration of 4-H2TMeP (40 µM), previously shown to be effective in vitro against these bacteria cultured in solution, was employed. Biofilms were treated with 4-H2TMeP and subjected to light irradiation for 30, 60, and 90min. Monocultures on canine skin samples were treated with 4-H2TMeP and irradiated for 30 (S. pseudintermedius), 60 (E. coli), or 60 and 90min (P. aeruginosa). Polycultures of S. pseudintermedius and E. coli were treated with light for 60 and 90min. The efficacy of aPDT was evaluated by plating light-exposed biofilms, mono and polycultures of bacteria obtained from skin samples exposed to light and kept in the dark. Colony-forming units were counted after 24h of incubation at 37°C. aPDT using 4-H2TMeP reduced bacterial concentrations of S. pseudintermedius and E. coli biofilms. Additionally, it significantly reduced bacterial concentrations cultivated on skin samples, with a particular emphasis on S. pseudintermedius. These findings indicate that aPDT with 4-H2TMeP is a promising alternative treatment against MDR bacteria in animal skin infections and should be further explored through in vivo research.

Sequential dual-locking strategy using photoactivated Pt(IV)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Novel near-infrared BODIPY-cyclodextrin complexes for photodynamic therapy

To meet the requirements of diagnosis and treatment, photodynamic therapy (PDT) is a promising cancer treatment with less side-effect. A series of novel BODIPY complexes (BODIPY-CDs) served as PDT agents were first reported to enhance the biocompatibility and water solubility of BODIPY matrix through the click reaction of alkynyl-containing BODIPY and azide-modified cyclodextrin (CD). BODIPY-CDs possessed superior water solubility due to the introduction of CD and their fluorescence emission apparently redshifted (>90 nm) on account of triazole units as the linkers compared to alkynyl-containing BODIPY. Moreover, all the BODIPY-CDs were no cytotoxicity toward NIH 3T3 in different drug concentrations from 12.5 to 200 μg/mL, and had a certain inhibitory effect on tumor HeLa cells. Particularly, BODIPY-β-CD exhibited high reactive oxygen species generation and excellent photodynamic therapy activity against HeLa cells compared to other complexes. The cell viability of BODIPY-β-CD was dramatically reduced up to 20% in the concentration of 100 μg/mL upon 808 nm laser irradiation. This architecture might provide a new opportunity to develop valuable photodynamic therapy agents for tumor cells.

Dressing and undressing MOF nanophotosensitizers to manipulate phototoxicity for precise therapy of tumors

Photodynamic therapy (PDT) is a clinically approved treatment for tumors, and it relies on the phototoxicity of photosensitizers by producing reactive oxygen species (ROS) to destroy cancer cells under light irradiation. However, such phototoxicity is a double-edged sword, which is also harmful to normal tissues. To manipulate phototoxicity and improve the therapy effect, herein we have proposed a dressing-undressing strategy for de-activating and re-activating therapy functions of photosensitizer nanoparticles. One kind of metal organic framework (PCN-224), which is composed of Zr(IV) cation and tetrakis (4-carboxyphenyl) porphyrin (TCPP), has been prepared as a model of photosensitizer, and it has size of ∼70 nm. These PCN-224 nanoparticles are subsequently coated with a mesoporous organic silica (MOS) shell containing tetrasulfide bonds (-S-S-S-S-), realizing the dressing of PCN-224. MOS shell has the thickness of ∼20 nm and thus can block 1O2 (diffusion distance: <10 nm), deactivating the phototoxicity and preventing the damage to skin and eyes. Furthermore, PCN-224@MOS can be used to load chemotherapy drug (DOX·HCl). When PCN-224@MOS-DOX are mixed with glutathione (GSH), MOS shell with -S-S-S-S- bonds can be reduced by GSH and then be decomposed, which results in the undressing and then confers the exposure of PCN-224 with good PDT function as well as the release of DOX. When PCN-224@MOS-DOX dispersion is injected into the mice and accumulated in the tumor, endogenous GSH also confers the undressing of PCN-224@MOS-DOX, realizing the in-situ activation of PDT and chemotherapy for tumor. Therefore, the present study not only demonstrates a general dressing-undressing strategy for manipulating phototoxicity of photosensitizers, but also provide some insights for precise therapy of tumors without side-effects. Statement of significancePhotosensitizers can generate reactive oxygen species (ROS) under light radiation to destroy cancer cells. However, this phototoxicity is a double-edged sword and also harmful to normal tissues such as the skin and eyes. To control phototoxicity and improve therapeutic efficacy, we prepared a PCN-224@MOS-DOX nanoplatform and proposed a dressing and undressing strategy to deactivate and reactivate the therapeutic function of the photosensitizer nanoparticles. The MOS shell can block the diffusion of 1O2, eliminate phototoxicity, and prevent damage to the skin and eyes. When injected into mice and accumulated in tumors, PCN-224@MOS-DOX dispersions are endowed with an endogenous GSH-driven undressing effect, achieving in situ activation of PDT and tumor chemotherapy.

The targeted photodynamic therapy of breast cancer with novel AS1411-indium(III) phthalocyanine conjugates

In the study, the novel indium(III) phthalocyanines containing 4-mercaptopyridine groups as substituents on the peripheral (Pc3) or non-peripheral (Pc8) tetra-and peripheral octa (Pc13) positions were synthesized. After then, the synthesized phthalocyanines were converted to their water-soluble derivatives that are Pc5, Pc10, and Pc15 by the quaternization of the nitrogen atoms on the substituents. These new phthalocyanines have been characterized by various spectroscopic methods such as FT-IR, 1HNMR, elemental analysis, UV–vis, MALDI-TOF mass spectra. Photochemical properties were also investigated for the synthesized phthalocyanines. In this study; quaternized derivatives were studied in DMSO and aqueous solutions, while non-quaternized derivatives were studied only in DMSO. The interaction between AS1411 and three phthalocyanines (Pc5, Pc10, and Pc15) was investigated using spectroscopic methods and electrochemical impedance spectroscopy technique combined with pencil graphite electrodes (PGEs). The cytotoxic activity of AS1411 and each phthalocyanine was investigated in the MCF-7 and doxorubicin (Dox) resistant MCF-7/DOX-R cell lines in the presence and absence of Dox. The photodynamic therapy (PDT) activity of Pc5, Pc10, and Pc15 and their AS1411 conjugates was investigated on MCF-7, MCF-7/DOX-R and MCF-10A cells. The IC50 values for MCF-7 cells were found as 1.1, 0.46, and 0.46 mM for Pc5 and 0.58, 0.34, and 0.32 mM for Pc5-AS1411 conjugate in the absence of irradiation and radiation with 7 J and 20 J. The values for MCF-7/DOX-R cells were found 0.81, 0.30, and 0.11 mM for Pc5 and 0.39, 0.12, and 0.15 mM for Pc5-AS1411 conjugate without irradiation and radiation with 7 J and 20 J, respectively. Apoptosis and cell imaging studies showed that conjugation of the phthalocyanines with AS1411 induced apoptosis in both cell lines and increases the intracellular entry of phthalocyanine Pc5.

Post-Operational Photodynamic Therapy of the Tumor Bed: Comparative Analysis for Cold Knife and Laser Scalpel Resection.

In this paper, we report on a study regarding the efficiency of the post-operational phototherapy of the tumor bed after resection with both a cold knife and a laser scalpel in laboratory mice with CT-26 tumors. Post-operational processing included photodynamic therapy (PDT) with a topically applied chlorin-based photosensitizer (PS), performed at wavelengths of 405 or 660 nm, with a total dose of 150 J/cm2. The selected design of the tumor model yielded zero recurrence in the laser scalpel group and 92% recurrence in the cold knife group without post-processing, confirming the efficiency of the laser scalpel in oncology against the cold knife. The application of PDT after the cold knife resection decreased the recurrence rate to 70% and 42% for the 405 nm and 660 nm procedures, respectively. On the other hand, the application of PDT after the laser scalpel resection induced recurrence rates of 18% and 30%, respectively, for the considered PDT performance wavelengths. The control of the penetration of PS into the tumor bed by fluorescence confocal microscopy indicated the deeper penetration of PS in the case of the cold knife, which presumably provided deeper PDT action, while the low-dose light exposure of deeper tissues without PS, presumably, stimulated tumor recurrence, which was also confirmed by the differences in the recurrence rate in the 405 and 660 nm groups. Irradiation-only light exposures, in all cases, demonstrated higher recurrence rates compared to the corresponding PDT cases. Thus, the PDT processing of the tumor bed after resection could only be recommended for the cold knife treatment and not for the laser scalpel resection, where it could induce tumor recurrence.

In vitro comparison of antifungal activity of conventional alcohol sprays and antimicrobial photodynamic therapy on acrylic denture resin.

Traditionally, alcohol sprays are used for disinfection of acrylic-base denture surfaces. A limited number of studies have assessed the role of antimicrobial photodynamic therapy (aPDT) in this regard; however, it remains debatable whether conventional alcohol sprays are superior to aPDT in terms of antifungal activity or vis versa. The aim of the present in vitro study is to compare the antifungal activity of conventional alcohol sprays and aPDT on acrylic denture resin. Individuals wearing complete dentures at least on one arch were included. Dentures were randomly divided into three groups. Groups 1-3 were disinfected with an alcohol-based antiseptic spray and aPDT, respectively. Assessment of oral yeast growth was done using swab samples. The culture mediums were incubated at 37∘C for 72 hours and viewed through a microscope. The numbers of colony forming units (CFU/ml) were determined. P< 0.05 were considered statistically significant. At baseline, the mean CFU/ml in Groups 1-3 were comparable. After disinfection, a statistically significant reduction in microbial CFU/ml was observed in Groups 1 (P< 0.05) and 2 (P< 0.05) compared with baseline. In Group 3, there was no difference in CFU/ml throughout the study. After disinfection, there was no difference in microbial CFU/ml in dentures in Groups 1 and 2. Conventional alcohol sprays are as effective as aPDT towards reducing oral yeasts CFU/ml on acrylic denture resin.

Biological Applications of The Newly Designed Phthalocyanine‐Modified Gold Nanorods

AbstractIn this study, a new di‐substituted phthalonitrile derivative namely 2‐[2‐{(3,5‐bis (trifluoromethyl) phenyl) ethynyl}‐4,5 dicyanophenyl] malonate was synthesized. The cycloteramerization of the resultant compound in the presence of the related metal salts resulted in a number of metal {M=Co, Mn, and Lu} phthalocyanines. The newly synthesized macromolecules were used for the functionalization of gold nanorods. To study the effect of modification and metal ion on the biological properties of the gold nanorods, the biological features of the phthalocyanines, phthalocyanine‐gold nanorod conjugates, and gold nanorods were examined by performing different biological approaches. In this study, the anti‐diabetic activities of fluorinated phthalocyanines and their gold nanorod conjugates were examined for the first time using pancreatic alpha‐amylase. The antioxidant activities of the studied nano/structures were analyzed using 2,2‐diphenyl‐1‐picrylhydrazil (DPPH) radical scavenging assay. Their antimicrobial and antimicrobial photodynamic therapy activities (APDT) were investigated, as well. They exhibited good DNA cleavage activities. The highest biofilm inhibition activities were obtained 97.49 and 91.53 % for 200 mg/L of nanoconjugate (7) against S. aureus and P. aeruginosa, respectively. All the studied biological candidates also displayed effective microbial cell viability inhibition activities against E. coli.

Influence of Passive Ultrasonic Irrigation of the Photosensitizer Used in Photodynamic Therapy on Microbial Reduction in the Root Canal System: An in Vitro Study.

The success of endodontic treatment is based on microbial reduction promoted by the interaction of chemical and mechanical procedures. Photodynamic therapy (PDT) is used as an adjunct to conventional treatment, with significant microbial reduction. This study aimed to evaluate the influence of passive ultrasonic irrigation (PUI) of the photosensitizer (PS) used in PDT on microbial reduction in the root canal system. Forty-five mesiobuccal root canals from extracted human mandibular molars that were inoculated with standard strains of Enterococcus faecalis, Candida albicans, and Streptococcus mutans for 21 days were selected. The root canals were prepared using the ProTaper Next system and randomly divided into 3 groups (n=15): 1) PDT: PDT alone; 2) PUI+PDT: PUI followed by PDT; and 3) PUI/PS+PDT: PUI of the PS followed by PDT. Microbiological samples were collected from the canals before and after using the protocols described above. The data were analyzed by analysis of variance (Tukey's test) at a significance level of 5%. Microbial counts before PDT, PUI+PDT, and PUI/PS+PDT did not differ significantly (P>0.05), showing methodological standardization in the microbial contamination of the root canal system. There was a significant reduction in microbial counts after PDT (61.05%), PUI+PDT (65.04%), and PUI/PS+PDT (68.58%) (P<0.01), but with no statistically significant difference between the three groups (P>0.05). Based on the present findings, it was concluded that the combination of PUI with PDT or PS activation did not influence microbial reduction achieved by PDT alone.

Activable Photodynamic DNA Probe with an "AND" Logic Gate for Precision Skin Cancer Therapy.

Photodynamic therapy (PDT) has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia, acquired resistance, phototoxicity, and so on. To address these issues, we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe (ADP). The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide (ASO) for recognition of Survivin mRNA. In the absence of the target, PDT remained quenched, thereby avoiding phototoxicity during circulation and nonselective distribution. With the aid of the aptamer, ADP achieved selective targeting of tumors. Upon internalization, ADP targeted recognized Survivin mRNA, triggering PDT activation, and releasing ASO to down-regulate Survivin expression and reverse tumor resistance. Consequently, the activable photosensitizers exhibited an "AND" logic gate, combining tumor-targeting delivery and tumor-related gene activation, thus enhancing its specificity. Additionally, the incorporation of hemin into the ADP provided catalase activity, converting tumor-abundant H2O2 into O2, thereby ameliorating tumor hypoxia. The resulting functionalized G-quadruplex/hemin-DNA probe complex demonstrated targeted delivery and activation, minimized side effects, and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models. This study offers a unique and promising platform for efficient and safe PDT, thus holding great potential for future clinical translation and improved cancer therapy.